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Puneet Tyagi, Christopher Hayden, Rajendra S. Kadam, Hu Yang, Uday B. Kompella; Hybrid Dendrimer-nanoparticle Formulation With Sustained In Vivo Efficacy Of Anti-glaucoma Drugs After Single Eye Drop Application. Invest. Ophthalmol. Vis. Sci. 2011;52(14):6691.
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The objective of this study was to formulate a hybrid dendrimer hydrogel- nanoparticle formulation to enhance and sustain delivery and efficacy of the anti-glaucoma drugs brimonidine and timolol maleate.
Dendrimer hydrogels comprising PAMAM dendrimer G3.0 coupled with PEG were synthesized. The cytotoxicity of dendrimer hydrogels in transformed human corneal epithelial cells (HCET) was assessed using a MTT assay. Poly (lactide-co-glycolide) polymer (PLGA) nanoparticles containing brimonidine and timolol maleate were prepared and assessed for drug loading and particle size. Two different formulations were prepared; one, wherein the plain drugs were dispersed in the dendrimer hydrogel and second, wherein the drugs were loaded in nanoparticles and then entrapped in the hydrogel. In vitro release of brimonidine and timolol maleate from the formulations was assessed in PBS pH 7.4 at 37ºC. The in vivo efficacy of these formulations in reducing intraocular pressure (IOP) was evaluated in rabbits after a single eye drop administration. The IOP was measured periodically up to 7 days post-dosing.
The MTT assay demonstrated that the HCET cells remained nearly 100% viable after 24 hour exposure to dendrimer hydrogels. The hydrogel formulation sustained the release of brimonidine and timolol maleate for approximately 3 days compared to 1.5 hours for co-incubation of both drugs in PBS. The hybrid dendrimer-nanoparticle system sustained drug delivery for more than a month and also enhanced drug uptake by HCET cells. The hybrid dendrimer-nanoparticle formulation maintained statistically significant IOP reduction for 7 days after a single eye drop administration compared to dendrimer hydrogel alone, which resulted in IOP reduction for only 3 days and plain drugs, which were effective for less than a day.
A hybrid dendrimer-nanoparticle formulation that allows sustained IOP reduction for at least a week after a single eye drop administration was developed.
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